The treatment of RLS
A strategy from:
Management of restless legs syndrome in primary care
Developed by RLS:UK
Non-pharmacological intervention
Good sleep hygiene and habits are helpful; advise patients to:
- sleep in a quiet, comfortable and cool environment
- Go to bed and wake at a regular hour (advise going to bed late and waking late)
- Avoid taking diuretics or caffeine before bedtime
During an attack, patients may find benefit from:
- Walking and stretching
- Bathing in hot or cold water
- Relaxation exercises (biofeedback or yoga)
- Distracting the mind
- Massaging affected limbs
Pharmacological treatment
The drugs used in RLS generally belong to the following classes:
A: Dopaminergic agents (Levodopa, dopamine agonists, amantadine; these drugs are also used in Parkinson's disease)
B: Anti-epilepsy drugs
C: Opoids
D: Benzodiazepines
E: Iron
F: Miscellaneous
A step-by-step approach to drug therapy may be useful:
- if intolerant to one agent, try an alternative dopamine agonist
- this approach is a good long-term option
- alleviates symptoms in at least 70% of patients
- any augmentation is mild
Levodopa, taken at bedtime, may be used if patients are intolerant to dopamine agonists
- 80-82% of patients treated will experience augmentation or rebound; therefore long-term use is limited
- useful for intermittent RLS
- use with caution in patients with angle-closure glaucoma, a history of malignant melanoma, cardiac disease or peptic ulcer disease
- Rotigotine transdermal patch may be particularly useful as it is administered once daily
- these drugs work by inhibiting hyperactivity in the nervous system that may be related to the symptoms
- Gabapentin is particularly useful for haemodialysis parients and for cases of painful RLS
Treatment strategies summarised
Dopaminergic drugs:
- Licensed for the treatment of moderate to severe RLS
- Good for periodic limb movements
- Low rates of augmentation
- Licensed for the treatment of moderate to severe RLS
- Good for periodic limb movements
- Low rates of augmentation
Dose range - 0.25-4 mg od
Rotigotine (transdermal patch)
- Licensed for moderate to advanced RLS
Dose range - 1-3 mg/24hrs
Cabergoline
- Related to cardiac valvulopathy
- Needs monitoring with echocardiography
- No longer recommended as first-line treatment
Dose range - 0.5-2 mg (single evening dose)
Pergolide
- Related to cardiac valvulopathy
- Needs monitoring with echocardiography
- No longer recommended as first-line treatment
Dose range - 0.1-0.75 mg od/bid
Bromocriptine
- Poor tolerance (preferably avoided)
- No longer recommended as first-line treatment
Dose range - 7.5 mg (divided dose)
Apomorphine
- Specialist monitoring required. Only recommended for severe RLS in Parkinson's disease
Dose range - 18-50 mg / 12hrs, overnight sc infusion
Levodopa DCI
- Rebound/augmentation
- Useful for intermittent RLS
Dose range - 100-600 mg evening or divided dose
Other drugs:
Gabapentin
- Quick dose escalation
- Useful second-line agent
- Painful RLS
- Useful in dialysis related RLS
Dose range - 300-2400 mg
Carbamazepine
- Single/divided doses
Dose range - 100-600 mg
Oxycodone
- Painful RLS
Dose range - 2.5-25 mg
Tramadol
- Painful RLS and insomnia
Clonazepam
- Useful for associated insomnia
Dose range - 0.5-2 mg evening dose
Triazolam
- As above
Dose range - 0.125-0.25 mg
Nitrazepam
- As above
Dose range - 2.5-10 mg
Clonodine
- Uraemia
Dose range - 0.15-2 0.9mg
Iron sulphate
- Iron deficiency (low ferritin levels)
Cause for concern
As the cause of RLS remains unclear there are hundreds of information sites in the internet, there are hundreds of individual accounts of “cure”, there are many claims to remedies. Many of these claims and information are unfounded, non-scientific and at times could be dangerous to health.
There have many scientific meetings in 2007-2008 which dealt with RLS and the associated disorder of PLM (periodic leg movement: a condition when the leg jerks either as you are about to doze of or when you are asleep). The most exciting discovery is that there appears to be more pointers towards a genetic basis to this condition with the independent discovery of three genes that may be related to RLS. It must be emphasised however, that as yet there are NO specific genetic tests that are available for RLS. These discoveries suggest potential genes that may be responsible for development of RLS in some and much work is needed in future. Firstly Winkelmann and colleagues described a gene called MEIS1 (on chromosome 2) associated with RLS and this gene tends to be involved in development of limbs. Thereafter, Stefansson and colleagues described another gene called BTBD9 (on chromosome 6). Finally, Winkelmann and colleagues also described another gene involved in the action of an enzyme nNOS. Potential implications of these discoveries are huge and in future this may open up new ways of identifying and treating RLS.
From the treatment point of view, drugs licensed specifically for treatment of RLS are pramipexole and ropinirole (marketed specifically for RLS as Adartrel). Both are useful but not all patients respond to these. Rotigotine, a skin patch that works by being applied once a day, has also been licensed for RLS. Like the other two, this is also a dopamine agonist drug and also is used primarily in Parkinson’s disease. IT IS WORTH NOTING HOWEVER, THAT USING THESE DRUGS IN RLS DOES NOT MEAN THAT THERE IS ANY RISK OF DEVELOPING PARKINSON’S DISEASE.
K Ray Chaudhuri
